US9975872B2ActiveUtilityPatentIndex 72

Processes for the preparation of (s)-3-(4-((4-(morpholinomethyl)benzyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione and pharmaceutically acceptable forms thereof

Assignee: CELGENE CORPPriority: Aug 9, 2012Filed: Mar 2, 2016Granted: May 22, 2018

Est. expiryAug 9, 2032(~6.1 yrs left)· nominal 20-yr term from priority

Inventors:TRAVERSE JOHN F ZHANG CHENGMIN FEIGELSON GREGG B COHEN BENJAMIN M LEONG WILLIAM W

A61P 37/00A61P 37/06A61K 31/5375A61K 31/4439C07D 401/04C07D 401/14A61P 29/00C07D 413/14A61P 27/02A61K 31/5377A61P 31/12

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Claims

Abstract

Provided are processes for the preparation of enantiomerically enriched or enantiomerically pure 3-(4-((4-(morpholinomethyl)benzyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, or a pharmaceutically acceptable form thereof.

Claims

exact text as granted — not AI-modified

What is claimed is: 
     
       1. A process to increase the enantiopurity of (S)-3-(4-((4-(morpholinomethyl)benzyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione hydrochloride or a solvate thereof, comprising recrystallization or trituration of a first sample of (S)-3-(4-((4-(morpholinomethyl)benzyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione hydrochloride or a solvate thereof in methanol, resulting in a second sample of (S)-3-(4-((4-(morpholinomethyl)benzyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione hydrochloride or a solvate thereof, wherein the second sample has a higher enantiomeric excess (ee) than the first sample. 
     
     
       2. The process of  claim 1 , wherein the enantiopurity is increased by recrystallization. 
     
     
       3. The process of  claim 1 , wherein the enantiopurity is increased by trituration. 
     
     
       4. The process of  claim 1 , wherein the enantiopurity is increased by 10% or more. 
     
     
       5. The process of  claim 4 , wherein the enantiopurity is increased by 20% or more. 
     
     
       6. The process of  claim 1 , wherein the first sample is in the anhydrous HCl salt form. 
     
     
       7. The process of  claim 1 , wherein the ee of the first sample is from 25% to about 90%. 
     
     
       8. The process of  claim 7 , wherein the ee of the first sample is from 50% to about 80%. 
     
     
       9. The process of  claim 1 , wherein the recrystallization or trituration occurs at a temperature of from about 10° C. to about 80° C. 
     
     
       10. The process of  claim 1 , wherein the ee of the second sample is no less than about 90%. 
     
     
       11. The process of  claim 10 , wherein the ee of the second sample is no less than about 95%. 
     
     
       12. The process of  claim 1 , wherein the first sample is (S)-3-(4-((4-(morpholinomethyl)benzyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione hydrochloride having an ee of 75%, the trituration occurs in methanol at 55° C., resulting in a second sample of (S)-3-(4-((4-(morpholinomethyl)benzyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione hydrochloride having an ee of 97.5%.

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